Article
Engineering, Biomedical
Yanqun Li, Jianhui Yue, Yuan Liu, Jun Wu, Min Guan, Di Chen, Haobo Pan, Xiaoli Zhao, William W. Lu
Summary: The study revealed that strontium promotes osteogenic differentiation of mesenchymal stem cells and balances stemness maintenance and osteogenic differentiation through asymmetric cell division. Strontium activates noncanonical Wnt signaling to regulate cell division and enhance osteogenic differentiation.
ACTA BIOMATERIALIA
(2021)
Article
Medicine, Research & Experimental
Dan Qin, Shenghui Liu, Yuanyuan Lu, Yi Yan, Jing Zhang, Shiyao Cao, Mi Chen, Ning Chen, Wendong Huang, Liqiang Wang, Xiangmei Chen, Lisheng Zhang
Summary: This study reveals the opposite regulatory effects of FXR and PPAR alpha on the fate of Lgr5(+) cells in the liver under physiological and pathological conditions. FXR activation promotes the expansion of Lgr5(+) cells, while PPAR alpha activation prevents their proliferation.
Article
Biochemistry & Molecular Biology
Swantje Liedmann, Xueyan Liu, Clifford S. Guy, Jeremy Chase Crawford, Diego A. Rodriguez, Duygu Kuzuoglu-Ozturk, Ao Guo, Katherine C. Verbist, Jamshid Temirov, Mark J. Chen, Davide Ruggero, Hui Zhang, Paul G. Thomas, Douglas R. Green
Summary: Activated CD8(+) T lymphocytes undergo heterogeneous differentiation, and this study reveals the mechanisms involved in establishing distinct T cell fate trajectories during the first division. The researchers discovered that dynein-dependent vesicular transport polarizes active TORC1 and eIF4F complexes towards the microtubule-organizing center (MTOC) at the proximal pole, leading to polarized translation of c-myc mRNA. Furthermore, the TORC1-eIF4A complex sorts preferentially to the proximal daughter cell upon division, facilitating asymmetric c-Myc synthesis. Disrupting eIF4A activity at first division skews long-term cell fate trajectories to memory-like function. These findings highlight the importance of localized translation and protein sorting in determining T cell fate.
Review
Cell Biology
Sydney Treichel, Marie-Dominique Filippi
Summary: Hematopoietic stem cells have the ability to self-renew or differentiate into various blood cell lineages. The cell fate decisions of self-renewal or differentiation must be tightly controlled to prevent diseases like bone marrow failure or leukemia. Studies have shown that the cell cycle length plays a crucial role in hematopoietic stem cell fate. Cell cycle kinetics, divisional history, asymmetric cell divisions, metabolic and organelle activity all have an impact on hematopoietic stem cell fate decisions.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Cell Biology
Timothy Patton, Zhe Zhao, Xin Yi Lim, Eleanor Eddy, Huimeng Wang, Adam G. Nelson, Bronte Ennis, Sidonia B. G. Eckle, Michael N. T. Souter, Troi J. Pediongco, Hui-Fern Koay, Jian-Guo Zhang, Tirta M. Djajawi, Cynthia Louis, Najoua Lalaoui, Nicolas Jacquelot, Andrew M. Lew, Daniel G. Pellicci, James McCluskey, Yifan Zhan, Zhenjun Chen, Kate E. Lawlor, Alexandra J. Corbett
Summary: Cell death mechanisms in T lymphocytes vary depending on their developmental stage, cell subset, and activation status. However, the cell death control mechanisms of mucosal-associated invariant T (MAIT) cells, a specialized T cell population, are not well understood. In this study, it was found that MAIT cells express high levels of key necroptotic machinery, RIPK3 and MLKL proteins. Surprisingly, the loss of RIPK3, but not MLKL or caspase-8, specifically increased the abundance of MAIT cells in various organs, indicating a cell-intrinsic regulation of MAIT cell accumulation by RIPK3 signaling.
CELL DEATH & DISEASE
(2023)
Article
Chemistry, Multidisciplinary
Sangpil Kim, Batakrishna Jana, Eun Min Go, Ji Eun Lee, Seongeon Jin, Eun-Koung An, Juyoung Hwang, Youjung Sim, Sehee Son, Dohyun Kim, Chaekyu Kim, Jun-O Jin, Sang Kyu Kwak, Ja-Hyoung Ryu
Summary: The study developed an intramitochondrial polymerization-induced self-assembly system for regulating the fate of cancer cells, inducing cell necroptosis by increasing ROS levels. This in situ polymerization system shows great potential for cancer treatment, including drug-resistant cancers.
Review
Immunology
Ines Sturmlechner, Abhinav Jain, Yunmei Mu, Cornelia M. Weyand, Jorg J. Goronzy
Summary: The defense against infectious diseases relies on the generation and maintenance of protective T cell memory. However, T cell differentiation in older adults tends to generate effector cells at the expense of memory and Tfh cells. This leads to poor vaccine responses, increased inflammatory state, and shorter life spans.
SEMINARS IN IMMUNOLOGY
(2023)
Article
Dermatology
Nuria Garcia-Diaz, Berta Casar, Ruth Alonso-Alonso, Laura Quevedo, Marta Rodriguez, Fulgencio Ruso-Julve, Anna Esteve-Codina, Marta Gut, Alejandro A. Gru, Maria Carmen Gonzalez-Vela, Ivo Gut, Jose Luis Rodriguez-Peralto, Ignacio Varela, Pablo Luis Ortiz-Romero, Miguel A. Piris, Jose Pedro Vaque
Summary: Research has shown that PKC theta plays a central role in activating malignant cutaneous T-cell lymphoma mechanisms through multiple routes. These mechanisms may serve as targets for specific therapies.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2022)
Article
Biology
Runxiang Qiu, Jun Wu, Brian Gudenas, Paul A. Northcott, Robert J. Wechsler-Reya, Qiang Lu
Summary: The study shows that targeting Kif20a can inhibit early cell cycle exit and premature neuronal differentiation of cerebellar granule neuron progenitors, suppressing tumor formation in medulloblastoma models. This suggests a potential novel avenue for developing anti-proliferation treatment for malignant brain tumors.
COMMUNICATIONS BIOLOGY
(2021)
Article
Cell Biology
Shawn P. Fahl, Alejandra Contreras, Anjali Verma, Xiang Qiu, Christelle Harly, Freddy Radtke, Juan Carlos Zuniga-Pflucker, Cornelis Murre, Hai-Hui Xue, Jyoti Misra Sen, David L. Wiest
Summary: This study reveals a regulatory axis where T cell receptor (TCR) signaling controls TCF1 expression, which in turn regulates gamma delta T lineage commitment and effector fate. The level of TCF1 expression plays a critical role in setting the threshold for gamma delta T lineage commitment and modulating effector fate.
Article
Multidisciplinary Sciences
Leonardo D. Estrada, Didem Agac Cobanoglu, Aaron Wise, Robert W. Maples, Murat Can Cobanoglu, J. David Farrar
Summary: This study investigates the role of ADRB2 signaling in regulating key transcriptional pathways during CD8 (+) T cell responses to infection. The findings demonstrate that ADRB2 signaling affects the expansion and differentiation of CD8 (+) T cells during the primary response to infection, as well as the expression of IL-2 and IL-2R alpha. Additionally, RNASeq analysis identifies over 300 differentially expressed genes that are selectively regulated in WT versus Adrb2(-/-) cells, contributing to major transcriptional pathways.
Article
Developmental Biology
Chee Kiang Ewe, Erica M. Sommermann, Josh Kenchel, Sagen E. Flowers, Morris F. Maduro, Pradeep M. Joshi, Joel H. Rothman
Summary: In the study, the core regulatory circuitry for endoderm development in Caenorhabditis elegans was shown to operate through a transcriptional cascade of six sequentially expressed GATA-type factors. This structure led to sequential redundancy and the phenotype strength could be predicted with a computational model based on transcriptional states. Key GATA factors were found to establish spatial regulatory state domains by repressing other fates.
Article
Plant Sciences
Pan Gong, Michiel Bontinck, Kirin Demuynck, Jolien De Block, Kris Gevaert, Dominique Eeckhout, Geert Persiau, Stijn Aesaert, Griet Coussens, Mieke Van Lijsebettens, Laurens Pauwels, Geert De Jaeger, Dirk Inze, Hilde Nelissen
Summary: SAMBA has been identified as a plant-specific regulator of the anaphase-promoting complex/cyclosome (APC/C) in Arabidopsis and maize. Two samba genome edited mutants in maize showed growth defects, with samba-1 representing a knockout allele and samba-3 producing a truncated protein that still interacted with APC/C but with altered activity. This suggests a dosage-dependent role for SAMBA in controlling developmental processes.
Article
Cell Biology
Liang Cao, Eva Morgun, Samantha Genardi, Lavanya Visvabharathy, Yongyong Cui, Haochu Huang, Chyung-Ru Wang
Summary: The study reveals the critical role of METTL14-dependent m(6)A modification in iNKT cell development and function. Loss of METTL14-dependent m(6)A modification leads to reduced numbers and impaired maturation of iNKT cells, as well as decreased responsiveness to stimulation.
Article
Cell Biology
Enric Mocholi, Laura Russo, Keshav Gopal, Andrew G. Ramstead, Sophia M. Hochrein, Harmjan R. Vos, Geert Geeven, Adeolu O. Adegoke, Anna Hoekstra, Robert M. van Es, Jose Ramos Pittol, Sebastian Vastert, Jared Rutter, Timothy Radstake, Jorg van Loosdregt, Celia Berkers, Michal Mokry, Colin C. Anderson, Ryan M. O'Connell, Martin Vaeth, John Ussher, Boudewijn M. T. Burgering, Paul J. Coffer
Summary: Upon antigen-specific TCR engagement, the generation of extramitochondrial pyruvate is crucial for acetyl-CoA production and subsequent histone acetylation remodeling. PDH-deficient T cells show that PDH-dependent acetyl-CoA production is a rate-limiting step during T cell activation. This study highlights the integration of metabolic and histone-modifying enzymes in CD4+ T cell activation, suggesting a potential therapeutic approach for regulating antigen-driven T cell activation.
Article
Multidisciplinary Sciences
Conor J. Kearney, Stephin J. Vervoort, Kelly M. Ramsbottom, Izabela Todorovski, Emily J. Lelliott, Magnus Zethoven, Lizzy Pijpers, Ben P. Martin, Timothy Semple, Luciano Martelotto, Joseph A. Trapani, Ian A. Parish, Nichollas E. Scott, Jane Oliaro, Ricky W. Johnstone
Summary: SUGAR-seq is a novel method that enables simultaneous detection of N-linked glycosylation, extracellular epitopes, and the transcriptome at the single-cell level, providing insights into cellular differentiation states. Integrated analysis using SUGAR-seq and glycoproteome identified tumor-infiltrating T cells with unique surface glycan properties that reflect their epigenetic and functional state.
Article
Biochemistry & Molecular Biology
Patrick O. Humbert, Tamara Zoranovic Pryjda, Blanka Pranjic, Andrew Farrell, Kohei Fujikura, Ricardo de Matos Simoes, Rezaul Karim, Ivona Kozieradzki, Shane J. F. Cronin, G. Gregory Neely, Thomas F. Meyer, Astrid Hagelkruys, Helena E. Richardson, Josef M. Penninger
Summary: This study identifies TSPAN6 as a tumor suppressor receptor that controls the initiation and progression of RAS-driven epithelial cancer. TSPAN6 suppresses tumor growth and metastasis by blocking EGFR-induced RAS activation.
Article
Multidisciplinary Sciences
Pei Kee Goh, Florian Wiede, Mara N. Zeissig, Kara L. Britt, Shuwei Liang, Tim Molloy, Nathan Goode, Rachel Xu, Sherene Loi, Mathias Muller, Patrick O. Humbert, Catriona McLean, Tony Tiganis
Summary: The tumor-suppressor gene PTPN2 is often diminished in a specific type of breast cancer. Surprisingly, the absence of PTPN2 in tumors or T cells can actually promote the recruitment and activation of T cells, leading to enhanced anti-tumor immunity. Targeting PTPN2 in tumor cells and T cells has therapeutic potential, as PTPN2 deficiency is associated with T cell infiltration and increased expression of PD-L1 in triple-negative breast cancers (TNBCs). Furthermore, deleting PTPN2 in mouse TNBC models can enhance T cell recruitment and PD-L1 expression, leading to suppressed tumor growth and improved efficacy of anti-PD-1 treatment. Additionally, deleting PTPN2 in both tumors and T cells can further facilitate T cell recruitment and activation, resulting in repression of tumor growth or even elimination of tumors dominated by exhausted T cells. Therefore, targeting PTPN2 in tumors and/or T cells can enhance T cell recruitment and alleviate inhibitory effects on T cells to combat TNBC.
Correction
Biochemistry & Molecular Biology
Patrick O. Humbert, Tamara Zoranovic Pryjda, Blanka Pranjic, Andrew Farrell, Kohei Fujikura, Ricardo de Matos Simoes, Rezaul Karim, Ivona Kozieradzki, Shane J. F. Cronin, G. Gregory Neely, Thomas F. Meyer, Astrid Hagelkruys, Helena E. Richardson, Josef M. Penninger
Article
Virology
Airah Javorsky, Patrick O. Humbert, Marc Kvansakul
Summary: Scribble is a crucial regulator of cell polarity during viral infections. The NS1 protein of influenza virus can target Scribble PDZ domains and disrupt the normal control of cell polarity. The study characterizes the binding affinities of different NS1 PDZ binding motifs to Scribble PDZ domains and provides insights into the structural basis of their interactions.
Article
Biochemistry & Molecular Biology
Airah Javorsky, Patrick O. Humbert, Marc Kvansakul
Summary: The study found that the interaction between the NS5 protein of TBEV and Scribble protein is through the PDZ3 domain of Scribble, contrary to the previous hypothesis. By determining the structural basis, these interactions provide a platform for studying the pathogenesis of TBEV and cell polarity signaling.
BIOCHEMICAL JOURNAL
(2022)
Article
Multidisciplinary Sciences
Saba Islam, Mirren Charnley, Guneet Bindra, Julian Ratcliffe, Jiangtao Zhou, Raffaele Mezzenga, Mark Hulett, Kyunghoon Han, Joshua T. Berryman, Nicholas P. Reynolds, Jeremy Engwirda
Summary: The authors report the presence of toxic clumps of protein in the COVID-19 virus that resemble amyloid assemblies found in Alzheimer's disease. They suggest that these clumps may play a role in the neurological symptoms observed in long-COVID.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Airah Javorsky, Janesha C. Maddumage, Emily R. R. Mackie, Tatiana P. Soares da Costa, Patrick O. Humbert, Marc Kvansakul
Summary: Scribble is a crucial regulator of cell polarity that interacts with Tax1 and disrupts cell polarity signaling, potentially promoting tumorigenesis.
Article
Biology
Anchi S. Chann, Mirren Charnley, Lucas M. Newton, Andrea Newbold, Florian Wiede, Tony Tiganis, Patrick Humbert, Ricky W. Johnstone, Sarah M. Russell
Summary: During T cell development, the process of TCR β chain genetic recombination is crucial. In this study, the selective inhibitor ACY1215 disrupted the fate determination at the beta-selection checkpoint, revealing a new stage characterized by the up-regulation of TCR co-receptors CD28 and CD2. Additionally, the up-regulation of CD5 and Lef1 during this stage reflects pre-TCR signaling and correlates with proliferation. These findings provide a refined model of beta-selection and highlight the importance of coordinated gene expression.
LIFE SCIENCE ALLIANCE
(2022)
Review
Biochemistry & Molecular Biology
Airah Javorsky, Patrick O. Humbert, Marc Kvansakul
Summary: Scribble is a scaffolding protein that regulates cell polarity, tumorigenesis and neuronal signalling. It interacts with viral effector proteins, leading to dysregulation of cell signalling pathways. This review focuses on the molecular details of Scribble and viral effector proteins interaction and provides insights into the regulation of Scribble-mediated polarity signalling.
BIOCHEMICAL SOCIETY TRANSACTIONS
(2023)
Meeting Abstract
Hematology
Lucas M. Newton, Christina B. Wolwer, Krystle Lim, Edwin D. Hawkins, Patrick O. Humbert
Article
Cell Biology
Anchi S. Chann, Ye Chen, Tanja Kinwel, Patrick O. Humbert, Sarah M. Russell
Summary: The regulation of daughter cell positioning involves the cooperation of polarity protein Scribble and E-cadherin. Scribble stabilizes E-cadherin and mediates spindle orientation, and then relocates to facilitate the formation of a new E-cadherin-based interface between the daughters, influencing cell positioning.
JOURNAL OF CELL SCIENCE
(2023)
Article
Multidisciplinary Sciences
Mirren Charnley, Amr H. Allam, Lucas M. Newton, Patrick O. Humbert, Sarah M. Russell
Summary: A critical stage in T cell development is beta-selection, where the T cell receptor beta (TCR beta) chain is generated and the T cell starts to acquire antigenic specificity. This study identifies E-cadherin as a critical cue within the developing T cell niche that facilitates T cell development. E-cadherin mediates cell-cell interactions and plays a role in the formation of the immunological synapse and alignment of the mitotic spindle during division, ultimately coordinating the beta-selection stage of T cell development.
Article
Multidisciplinary Sciences
Bryce Z. Stewart, Tatyana Mamonova, W. Bruce Sneddon, Airah Javorsky, Yanmei Yang, Bin Wang, Thomas D. Nolin, Patrick O. Humbert, Peter A. Friedman, Marc Kvansakul
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)